It is also used to treat rheumatoid arthritis, and there are a total of approximately 2.1 million patient-years of exposure in patients with this condition, suggesting an excellent safety and tolerability profile.

Teriflunomide is a once-daily, orally available immunomodulator that reversibly inhibits the mitochondrial enzyme dihydroorotate dehydrogenase, which plays an important role in pyrimidine synthesis needed for DNA replication. By hindering T- and B-cell proliferation and function in response to autoantigens, the drug functions as a disease-modifying therapy for MS. However, it does not affect the replication and function of hematopoietic cells, memory T cells, or other cells living on their pyrimidine pool through the salvage pathway.

The boxed warning points out that, based on animal studies, the drug may be teratogenic, important because many patients with MS are women of childbearing age.

In the current study, children with URIs and nocturnal cough were given either 1 of 3 different honey products or a placebo 30 minutes before bedtime, based on a double-blind randomization plan. The primary outcome evaluated was a subjective change in cough frequency, based on parent surveys. Secondary outcomes measured included a change in cough severity, the effect of the cough on sleep for both the child and the parent, and the combined score on the pre- and postintervention surveys.

Herman Avner Cohen, MD, from the Pediatric Ambulatory Community Clinic, Petach Tikva, Israel, and colleagues compared symptom scores for each treatment group before and after the intervention and found that patients in all 3 honey groups demonstrated significant improvement compared with patients treated with placebo. There were no significant differences among the different types of honey.

“The results of this study demonstrate that each of the 3 types of honey (eucalyptus, citrus, and labiatae) was more effective than the placebo for the treatment of all of the outcomes related to nocturnal cough, child sleep, and parental sleep,” the authors write.

The researchers enrolled 300 children with URIs, aged 1 to 5 years, who were seen at 1 of 6 general pediatric community clinics between January 2009 and December 2009. Patients were eligible if they had a nocturnal cough attributed to the URI. Children were excluded if they had symptoms of asthma, pneumonia, laryngotracheobronchitis, sinusitis, and/or allergic rhinitis. Patients who used any cough or cold medication or honey in the previous 24 hours were also excluded.

Parents were asked to evaluate the children the day of presentation, when no medication had been given, and then again the day after a single dose of 10 g of eucalyptus honey, citrus honey, labiatae honey, or placebo (silan date extract) had been administered before bedtime. Pre- and postintervention subjective assessments were obtained using a 5-item Likert-scale questionnaire regarding the child’s cough and sleep difficulty. Only those children whose parents rated severity as at least a 3 (on a 7-point scale) for at least 2 of the 3 questions related to nocturnal cough and sleep quality on the preintervention questionnaire were included.

Of the 300 patients enrolled, 270 (89.7%) completed the single-night study. The median age of these children was 29 months (range, 12 – 71 months). There was no significant age difference among the treatment groups. Symptom severity was also similar among all 4 treatment groups.

Adverse events were reported for 5 patients and included stomachache, nausea, and vomiting and were not significantly different between the groups.

The drug was given priority review by the FDA for this indication, a statement from Pfizer notes, and brings to 5 the number of approved indications for pregabalin in the United States; others include diabetic neuropathy, postherpetic neuralgia, fibromyalgia, and partial-onset seizures in adults with epilepsy who take 1 or more drugs for seizures.

More than 100,000 patients, or about 40% of patients with traumatic or nontraumatic spinal cord injury in the United States, develop neuropathic pain associated with the injury. “Neuropathic pain associated with spinal cord injury can be severely debilitating and may significantly hinder rehabilitation and the ability to regain function,” the statement said.

Neuropathic pain can be experienced above, at, or below the level of injury and is typically not confined to one area of the body, the statement notes. “Approximately one-third of spinal cord injury patients report below-level neuropathic pain that is severe or excruciating,” they write. It can be begin as soon as 2 weeks after the injury and persist up to 25 years.

The approval is based on results of 2 randomized, double-blind phase 3 trials comparing flexibly dosed pregabalin (150 to 600 mg/d) with placebo in 357 patients. Patients were allowed to continue other medications, including other pain medications, such as nonsteroidal anti-inflammatory drugs, opioids, and nonopioid medications. One study included only patients with traumatic spinal cord injury, and the other included about 5% of patients with nontraumatic injuries.

Studies showed pregabalin significantly reduced neuropathic pain between baseline and 12 and 16 weeks in each study, respectively, vs placebo. More patients taking pregabalin showed 30% and 50% reductions in pain than those taking placebo. For some patients, the reduction in pain was significant as soon as week 1 and continued throughout the trial, the statement notes.

The most common adverse events with pregabalin were somnolence, dizziness, dry mouth, fatigue, and peripheral edema. Antiepileptic drugs, including pregabalin, increased the risk for suicidal thoughts or behaviors. There have been postmarketing reports of angioedema and hypersensitivity with pregabalin, the release adds. Other reactions include blurred vision, weight gain, constipation, euphoric mood, balance disorder, increased appetite, and abnormal thinking (primarily difficulty with concentration and attention).

“This milestone represents an important opportunity for physicians to more effectively manage the debilitating neuropathic pain that often accompanies spinal cord injury,” said clinical study investigator Diana Cardenas, MD, MHA, professor and chair, department of rehabilitation medicine, University of Miami Miller School of Medicine and chief of service for rehabilitation medicine and medical director of Jackson Rehabilitation Hospital, Miami, Florida, in the Pfizer statement. “Given the clinical challenges of investigating neuropathic pain in this patient population, any advancements in treatment are welcome by physicians and patients alike.”

The Food Safety and Standards Act. 2006 has come into force with effect from 05^th August. 2011. It defines a Food Business Operator (FBO) as a person engaged in the business of food manufacture, processing, packaging, transportation, distribution, storage and import etc. and includes food services, catering services and sale of food or food ingredients.

REGISTRATION AND LICENSING

• All Food Business Operators (FBO) in the country have to be registered or licensed in accordance with the cutoff limits laid down in the Food Safety and Standards (Licensing and Registration of Food Business) Regulations, 2011.
• A milk producer whose production capacity of the Milk & Meat Products is less than 100 Kg/Ltr. per day, or is handling milk less than 500 Ltr. per day, meat or meat products producer in the capacity for slaughter of maximum 2 large animal or 10 small animals or 50 poultry birds per day or any other FBO where annual turnover is less than Rs 12 Lakh is termed as Petty Food Business Operator (PFBO) and is required to be registered.
• Schedule 1 of the Regulations defines the businesses that will be licensed by FSSAI Regional offices. All other businesses will have to obtain license from the local District Designated Officer of the state.
• Application can be filed online at foodlicensing.fssai.gov.in for central licensing.

EXISTING LICENSEES

■                    Convert your existing food licenses / registration into FSSAI license Registration before 5^th August, 2012

■                    No license registration fee will have to be paid for the remaining period of the validity of the earlier license or registration.

■                    All FBO should have valid license at all time.

• If the existing license registration has expired after 5″ August. 2012 apply for its renewal immediately.

■                    No pre – inspection required.

■                    A New FSSAI license number will be issued.

• Comply with existing provisions of Food Safety and Standards (Licensing and Registration of Food Business) Regulations, 2011.

For further details visit fssai.gov.in or Dial-Toll free helpline 1800112100

Issued in Public interest by

Food Safety and Standards Authority of India

FDA Bhawan, Kotla Road,

New Delhi – 110002

Endogenous Cushing’s syndrome is a serious, debilitating and rare multisystem disorder.

It is caused by the overproduction of cortisol (a steroid hormone that increases blood sugar levels) by the adrenal glands. This syndrome most commonly affects adults between the ages of 25 and 40.

Mifepristone blocks the binding of cortisol to its receptor. It does not decrease cortisol production but reduces the effects of excess cortisol, such as high blood sugar levels.

Mifepristone is approved for use in patients with endogenous Cushing’s syndrome who have type 2 diabetes or glucose intolerance and are not candidates for surgery or who have not responded to prior surgery.

It should never be used by pregnant women. Although pregnancy is an extremely rare occurrence in Cushing’s syndrome patients because of the suppressive effect of excess cortisol on female reproductive function.

The most common side effects experienced with mifepristone  are nausea, fatigue, headache, arthralgia, vomiting, swelling of the extremities, dizziness and decreased appetite.

Other side effects of mifepristone include adrenal insufficiency, low potassium levels, vaginal bleeding and a potential for heart conduction abnormalities.

There are no other approved medical treatment for this debilitating form of Cushing’s syndrome.

The US Food and Drug Administration (FDA) warned that patients taking statins may face a “small increased risk” of higher blood-sugar levels and diabetes.

Statins, when used with diet and exercise, help to lower a person’s “bad” cholesterol (low-density lipoprotein cholesterol). Statins include blockbusters like Lipitor (atorvastatin) – the world’s largest selling drug with annual sales of around $12 billion – and other brands and generic versions like simvastatin, pravastatin and rosuvastatin. The issue has been debated for years with several studies also conducted to research whether there was an increased risk of diabetes by taking statins.

The FDA wants drug companies to add these warnings on labels of these cholesterol-lowering drugs. The drugs regulator here is expected to follow suit within a few months in India too, experts say. There are over a dozen domestic companies including Ranbaxy, Dr Reddy’s, Cipla, Glenmark, Sun Pharma, Lupin, USV, Zydus and Torrent selling generic versions of the drug.

But the FDA said it also wants to assure users that these medications continue to provide an important health benefit of lowering cholesterol.

This randomized controlled, open-label trial compares the effect of bedtime vs morning administration of BP medications on a composite of cardiovascular disease (CVD) outcomes and BP control.

According to Dr. Hermida and colleagues, “treatment at bedtime is the most cost-effective and simplest strategy of successfully achieving the therapeutic goals of adequate asleep BP reduction and preserving or re-establishing the normal 24-hour BP dipping pattern.”

The authors suggest that a potential explanation for the benefit of nighttime treatment may be associated with the effect of nighttime treatment on urinary albumin excretion levels. “We previously demonstrated that urinary albumin excretion was significantly reduced after bedtime, but not morning, treatment with valsartan,” they note. In addition, this reduction was independent of 24-hour changes of BP, but correlated with a decline in BP during sleep.

Refer: J Am Soc Nephrol. Published online October 24, 2011

Indacaterol maleate is a new molecular entity in the β₂-adrenergic agonist class that helps relax muscles around lung airways to prevent COPD symptoms, such as wheezing and breathlessness. The FDA stated that the long-acting drug is not intended to treat asthma or COPD symptoms that come on fast and strong.

Common adverse effects (> 2% and more common than placebo) are runny nose, cough, sore throat, headache, and nausea.

Indacaterol maleate will carry a boxed warning that, like other long-acting β₂-adrenergic agonists (LABAs), may increase the risk for asthma-related death.

Without use of a long-term asthma control medication, indacaterol maleate and all LABAs are contraindicated in patients with asthma. Indacaterol maleate should not be started in patients with acutely deteriorating COPD, nor should it be used to relieve acute symptoms, which should be managed with concomitant short-acting β₂-agonists.

An FDA advisory panel in March recommended approval of indacaterol maleate after 6 confirmatory clinical trials demonstrated the drug’s safety and efficacy. The trials included nearly 5500 patients 40 years and older with COPD who had smoked at least 1 pack of cigarettes for 10 years and exhibited moderate to severe decreases in lung function.

During the advisory panel meeting, John Walsh, the president of the nonprofit COPD Foundation, said that getting patients to faithfully take twice-daily LABAs is a challenge.

Clinical Use

• The FDA approved indacaterol maleate as a once-daily bronchodilator to prevent COPD symptoms, such as wheezing and breathlessness. Dosage is 75 μg inhaled once daily every day, which should increase compliance relative to twice-daily inhalers. It is not intended for acute relief of COPD exacerbations.
• Common adverse effects seen with use of indacaterol maleate are runny nose, cough, sore throat, headache, and nausea. It will carry a boxed warning that the risk for asthma-related death may be increased. There are several significant drug interactions.
• Indacaterol maleate is pregnancy Category C. It should be used during labor only in those patients in whom the benefits clearly outweigh the risks, and caution is warranted when indacaterol maleate is administered to breast-feeding women. Indacaterol maleate is not indicated for use in children. No adjustment of dosage is warranted in geriatric patients nor in patients with mild and moderate hepatic impairment.

Valproate products are approved to treat seizures and manic or mixed episodes associated with bipolar disorder (manic-depressive disorder), and to prevent migraine headaches. They are also used off-label for other conditions, particularly other psychiatric conditions.

“FDA has evaluated all available evidence to date, and will be adding information about the risk of lower cognitive test scores to the valproate product labels in the Warnings and Precautions section, the Use in Specific Populations: Pregnancy section, and to the Medication Guides that are being developed for the valproate drug products,” the alert notes.

The FDA previously warned pregnant women and women of childbearing age about valproate use during pregnancy because of known teratogenic effects, and valproate products are assigned to Pregnancy Category D. The FDA also released an Information for Healthcare Professionals communication in December 2009 on the risk for neural tube birth defects after exposure to valproate products during pregnancy.

Their conclusion is based on epidemiologic studies showing that children exposed to valproate in utero tend to score lower on cognitive testing than children exposed to other agents.

The primary study supporting the conclusion is based on the well-known work of Kimford Meador, MD, from Emory University in Atlanta, Georgia, and investigators in the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study. The FDA has used the data from testing performed when the children were age 3; these results were published in the New England Journal of Medicine in 2009.